Alcohol-induced vascular damage of brain is ameliorated by administration of magnesium.
Ethanol ingestion can cause irreversible neuronal and vascular damage in the brain and stroke-like events. Using an intact in vivo rat brain (pial) model, TV image-intensification, cultured cerebral vascular muscle cells, digital-image analysis, and a novel Mg2+ ion-selective electrode to measure extracellular ionized Mg2+, studies were designed to determine whether: 1) perivascular or systemic administration (i.v. or intra-arterial) of magnesium aspartate HCI (MgA) exert vasodilator effects on arterioles (65-130 microm o.d.) and venules (60-135 microm); 2) nonvasodilator doses of MgA could modify vascular spasms induced by BaCl2 and ethanol; 3) nonvasodilator doses of MgA could ameliorate or prevent the cerebral vascular damage induced by high doses of ethanol; and 4) ethanol depletes cerebral vascular muscle of intracellular Mg ions ([Mg2+]i). Perivascular application of MgA (0.01-100 micromol) produced dose-dependent vasodilatation of cerebral arterioles and venules; arterioles yielded greater vasodilator responses compared to venules. Nonvasodilator doses of Mg (1.0, 4.0 micromol/min), administered i.v. or intra-arterially, into a branch of the internal carotid artery, prevented: 1) the spasmogenic actions of ethanol and Ba2+; and 2) the vasculotoxic actions (rupture of postcapillary venules and focal hemorrhages) of ethanol. In addition, ethanol depleted cerebral vascular muscle cells of [Mg2+]i; blood levels of ionized Mg2+ rose after IP ethanol. Despite the fact that systemic infusion of low nonvasodilator doses did not result in dilatation of the pial arterioles and venules, plasma total and ionized Mg rose 18-230%, depending upon dose of MgA and time of plasma sampling. These data support the idea that Mg2+ can act as a local vasodilator on brain microvessels and possess antispasmodic properties on brain arterioles and venules. In addition, our results indicate that Mg may possess some unique cerebral vascular protective properties against the vasculotoxic effects of ethanol. Lastly, these findings suggest ethanol-induced cerebrovasospasm and vascular damage appear to be associated with a rapid loss of [Mg2+]i from cerebral vascular muscle cells.
Ema
M
M
Department of Physiology, State University of New York, Health Science Center at Brooklyn, 11203, USA.
Gebrewold
A
A
Altura
B T
BT
Zhang
A
A
Altura
B M
BM
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001224:Aspartic Acid / Q000494:pharmacology; D017609:Barium Compounds / Q000009:adverse effects; D001921:Brain / Q000098:blood supply*; D002339:Carotid Arteries; D002478:Cells, Cultured; D002561:Cerebrovascular Disorders / Q000139:chemically induced* / Q000517:prevention & control*; D002712:Chlorides / Q000009:adverse effects; D004285:Dogs; D000431:Ethanol / Q000494:pharmacology*; D005268:Femoral Vein; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008274:Magnesium / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects; D014699:Venules / Q000187:drug effects / Q000502:physiology
D017609:Barium Compounds; D002712:Chlorides; C024986:barium chloride; D001224:Aspartic Acid; D000431:Ethanol; D008274:Magnesium